Several decades of research indicate that the central nervous system plays an important role in the precise regulation of food intake and body weight. Recently several hypotheses have emerged which attempt to specify the anatomical systems that perform these regulatory functions. The systems on which these hypotheses focus are the catecholamine and indolamine containing neurons that originate in the midbrain and pons and terminate extensively in the hypothalamus. In the studies proposed, a comparative approach will be used to examine the role of the monoamines, in particular the catecholamines, in the major animal models of obesity. In normal rodents, toxins such as goldthioglucose and monosodium 1-glutamate will be used to induce obesity. The effects of these treatments on specific monoamine systems will be evaluated. In genetically obese rodents, the relationship of spontaneously occurring obesity to monoamine function will be examined. Several types of obese mutants are known to have altered levels of brain or pituitary monoamines. The generality of this finding will be investigated. In addition, the effects on body weight of lesions that alter monoamine levels will be examined in these mutants. Finally, the effects on monoamines of treatments which alter body weight or suppress food intake will also be examined.